tag:blogger.com,1999:blog-1812431336777691886.post8753849014338666010..comments2024-02-29T03:57:00.088-05:00Comments on The Mermaid's Tale: Thoughts on the latest schizophrenia genetics reportAnne Buchananhttp://www.blogger.com/profile/09212151396672651221noreply@blogger.comBlogger4125tag:blogger.com,1999:blog-1812431336777691886.post-82399371866719883082016-02-17T08:40:44.630-05:002016-02-17T08:40:44.630-05:00Thanks for making this comment. The problem is th...Thanks for making this comment. The problem is the hunger for attention by investigators and for Big Stories by the news media. The real story here, if there is one, is the potential functional lead to something involved in relevant brain function. Why this should involve Complement, which has been thought (I thought, at least) to be about immunity, is interesting. But I cant' guess what it might mean with any degree of knowledgeability. The fact that these causal effects are so small should also have been said, however, not just the impression that this accounts for a high fraction of schizophrenia or high risk to the individual.Ken Weisshttps://www.blogger.com/profile/02049713123559138421noreply@blogger.comtag:blogger.com,1999:blog-1812431336777691886.post-27927016025612177552016-02-17T08:32:57.160-05:002016-02-17T08:32:57.160-05:00I find it incredibly scary that the lead author wa...I find it incredibly scary that the lead author was quoted in the New York Times as saying that the risk variant has a relative risk of 1.25, which he said means that the risk of carriers is 0.0125 instead of 0.01... While this itself is a trivial effect, it is complete bollocks... Based on the allele frequencies of the different structural forms of C4 from the paper, and given they assigned the relative risk of 1.0 to the BS form, meaning that all risks are relative to that one, not to the population prevalence, the actual risk of carriers of the AL-AL form would be 0.0107, not 0.0125, while the risk of carriers of the RARE BS form would be reduced from 0.01 to 0.0084... Effectively the point is that 0.0107 is a MUCH tinier increase over the 0.01 population risk than 0.0125, and its kind of scary that the lead author doesn't understand his own statistics, or at least that he conveyed it so inaccurately to the media.....Joseph D. Terwilligerhttps://www.blogger.com/profile/09748475850511980937noreply@blogger.comtag:blogger.com,1999:blog-1812431336777691886.post-9340461930720257352016-02-09T12:38:00.868-05:002016-02-09T12:38:00.868-05:00If C4 CNV is as common as the report says, I would...If C4 CNV is as common as the report says, I would be surprised if the same is not found in other species, even the mouse (surely that's known, though not by me). It seems to be too prevalent not to be a part of long-term copying processes. Recurrent 'mutation' would mean, I think, slippage and so on, not nucleotide changes. That sort of thing happens once multiple adjacent copies of a gene arise, and there are plenty of other genomic precedents.<br /><br />Anyway, it's an empirical question how widespread it is among mammals. Mild negative selection might remove copies, but new slippage events would recreate new multiple copies. Mild selection might just keep the system from having too many copies, or something like that. Or population dynamics could over-ride the effects of mild selection. And there may not be any systematically negative selection for the SZ trait now, or in the past. Some have argued that such behavioral traits could even have an advantage in securing mates, etc. That's been a long-standing point of view, whether right or wrong.Ken Weisshttps://www.blogger.com/profile/02049713123559138421noreply@blogger.comtag:blogger.com,1999:blog-1812431336777691886.post-10442907477118564312016-02-09T12:30:23.042-05:002016-02-09T12:30:23.042-05:00I'd argue that C4 copy number variation is not...I'd argue that C4 copy number variation is not necessarily evolutionarily old but generated by recurrent mutation, which would explain different copy number alleles on different SNP haplotypes, and also why mild negative selection has not removed the variation.Ed Holloxnoreply@blogger.com